Dwarf beech : yesterday, today, tomorrow

Det fanns något lockande i ett ovanligt träd som nästan utrotades under 1700-talet, som varit andligt laddat i det förflutna och i att världens största bestånd av denna trädtyp kallad vresbok (Fagus sylvatica f. tortuosa) eller Freak beech som Kraft (1968) kallade den, växer geografiskt nära mig i Skåne. Detta examensarbete handlar om att få kunskap om vresboken och förmedla vad den egentligen är och har betytt för människan, och att få en överblick över dess utbredning geografiskt, historiskt och idag, samt få klarhet i varför den inte används mer i offentliga sammanhang idag. Under mina fältundersökningar har jag sett att trots att den växer i utmarker där det ofta är stenigt i sluttningar, ser markfloran och ståndorten ganska olika ut. Detta menar jag tyder på att det viktigaste för vresbokens fortlevnad inte är själva ståndorten, utan att den helt enkelt växer där den fått vara ifred och fått stå kvar och det är antagligen på marker som människan förr inte kunde bruka för odling och slåtter utan hörde till utmarkernas betesområden. Varför den inte används i offentliga sammanhang kan jag utifrån mina fältbesök och intervjuer se två orsaker till. Den största är att den är så långsamväxande. Den är även oförutsägbar ur förökningssynpunkt. Vissa hävdar till och med att det är omöjligt att föröka vresboken från frö. Den andra anledningen som jag sett då jag besökte den enda vresboken jag känner till i offentliga sammanhang, på Uppåkra Kyrkogård, är att den är oförutsägbar i sitt växtsätt. Det är svårt att veta vilken form och storlek vresboken kommer få. På kyrkogården hade de planterat en planta på en gravplats, och på 100 år hade den brett ut sig över fyra gravplatser och totalt skuggat ut all annan vegetation. Den hade varit svårt att tukta den med beskärning så att den höll sig på den ursprungliga gravplatsen då den hade tappat sin naturliga intressanta växtform. Angående föryngringen har jag hittat gott om unga vresbokar på lokalerna jag undersökt och inventerat. Om platserna sköts rätt, via selektiv röjning av sly och fällning av en del skuggande och höga träd, tror jag att de unga vresbokar jag hittat har en god chans att växa och leva vidare, särskilt då majoriteten av lokalerna är naturreservat och skötselplaner finns upprättade för vresbokarnas bästa

Cesarean delivery, preterm birth and risk of food allergy : nationwide Swedish cohort study of over 1 million children

Background & Objectives: Little is known about early life risk factors for food allergy in children. We examined the association between perinatal characteristics and future risk of food allergy in offspring. Methods: This nationwide Swedish cohort study of 1,086,378 children born in Sweden in 2001-2012 used prospectively recorded data from health care registers. Using Cox regression, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between perinatal characteristics (e.g. caesarean delivery, preterm birth) and food allergy as defined by diagnoses in the National Patient Register, adjusting for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index and asthma/pulmonary disease). Results: During the 13-year follow-up, 26,732 children (2.5%) were diagnosed with food allergy. Food allergy was positively associated with caesarean delivery (HR=1.21; 95%CI=1.18-1.25), large for gestational age (HR=1.15; 95%CI=1.10-1.19) and low 5-minute Apgar score (HR=1.22, 95CI=1.10-1.36) but negatively associated with very preterm birth (<32 weeks of gestation: HR=0.74; 95%CI=0.56-0.98). No association was found between food allergy and moderately preterm birth, low birth weight or small for gestational age. Risk estimates were similar when the outcome was restricted to two records of diagnosed food allergy. In 1,000 children undergoing caesarean delivery, an extra 5 developed food allergy compared with the reference group, suggesting that 17% of food allergy in children born with caesarean delivery can be explained by this exposure (attributable fraction). Conclusions: Caesarean delivery was associated with increased risk of food allergy, whereas very preterm birth with decreased risk.NoneAccepte

Blood Pressure in 6-Year-Old Children Born Extremely Preterm

Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.Peer reviewe

The Preterm Heart in Childhood : Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births

Background-Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. Methods and Results-In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. Conclusions-Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.Peer reviewe

Interactions between Glutathione S-Transferase P1, Tumor Necrosis Factor, and Traffic-Related Air Pollution for Development of Childhood Allergic Disease

BACKGROUND: Air pollutants may induce airway inflammation and sensitization due to generation of reactive oxygen species. The genetic background to these mechanisms could be important effect modifiers. OBJECTIVE: Our goal was to assess interactions between exposure to air pollution and single nucleotide polymorphisms (SNPs) in the beta2-adrenergic receptor (ADRB2), glutathione S-transferase P1 (GSTP1), and tumor necrosis factor (TNF) genes for development of childhood allergic disease. METHODS: In a birth cohort originally of 4,089 children, we assessed air pollution from local traffic using nitrogen oxides (traffic NO(x)) as an indicator based on emission databases and dispersion modeling and estimated individual exposure through geocoding of home addresses. We measured peak expiratory flow rates and specific IgE for inhalant and food allergens at 4 years of age, and selected children with asthma symptoms up to 4 years of age (n = 542) and controls (n = 542) for genotyping. RESULTS: Interaction effects on allergic sensitization were indicated between several GSTP1 SNPs and traffic NO(x) exposure during the first year of life (p(nominal) &lt; 0.001-0.06). Children with Ile105Val/Val105Val genotypes were at increased risk of sensitization to any allergen when exposed to elevated levels of traffic NO(x) (for a difference between the 5th and 95th percentile of exposure: odds ratio = 2.4; 95% confidence interval, 1.0-5.3). In children with TNF-308 GA/AA genotypes, the GSTP1-NO(x) interaction effect was even more pronounced. We observed no conclusive interaction effects for ADRB2. CONCLUSION: The effect of air pollution from traffic on childhood allergy appears to be modified by GSTP1 and TNF variants, supporting a role of genes controlling the antioxidative system and inflammatory response in allergy

The PELICAN (Prematurity's Effect on the Lungs In Children and Adults Network) ERS clinical research collaboration: understanding the impact of preterm birth on lung health throughout life

An estimated 15 million babies (∼11%) are born preterm each year (before 37 weeks of gestation), the rates of which are increasing worldwide [1]. Enhanced perinatal care, including antenatal corticosteroids, postnatal surfactant and improved respiratory management, have markedly improved survival outcomes since the 1990s, particularly for babies born very preterm (<32 weeks gestation) [1]. However, long-term pulmonary sequelae are frequent in preterm survivors and ongoing clinical management is often required. Development and severity of bronchopulmonary dysplasia (BPD), a chronic lung condition diagnosed during the neonatal period [2], is a key determinant of long-term adverse outcomes of prematurity

Changes of DNA methylation are associated with changes in lung function during adolescence

Background Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs. Methods Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped. Results For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development. Conclusions The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in female

Clinical implications of airway obstruction with normal or low FEV 1 in childhood and adolescence.

Background: Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV1 (classic) or a normal FEV1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear. Aims: To investigate the association between airway obstruction with a low or normal FEV1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR). Methods: In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV1:FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV1 <LLN) or dysanaptic (FEV1 ≥LLN) obstruction. Cross-sectional and longitudinal associations between these two types of obstruction and respiratory health outcomes were estimated by cohort-adjusted logistic regression on pooled data. Results: The prevalence of classic obstruction at ages 8, 12 and 16 in the two cohorts was 1.5%, 1.1% and 1.5%, respectively. Dysanaptic obstruction was slightly more prevalent: 3.9%, 2.5% and 4.6%, respectively. Obstruction, regardless of FEV1, was consistently associated with higher odds of asthma (dysanaptic obstruction: OR 2.29, 95% CI 1.40 to 3.74), wheezing, asthma medication use and BHR compared with the normal lung function group. Approximately one-third of the subjects with dysanaptic obstruction in childhood remained dysanaptic during adolescence. Clinical implications: Children and adolescents with airway obstruction had, regardless of their FEV1 level, a higher prevalence of asthma and wheezing. Follow-up and treatment at these ages should be guided by the presence of airway obstruction

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against &gt;100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations